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    • The present work has implications for our thinking

    2024-04-29

    The present work has implications for our thinking about the effects of antidepressant (e.g. SSRIs) use on maternal care in depressed mothers which consist of approximately 10–20% of all mothers (Gjerdingen and Yawn, 2007, Susser et al., 2016), and more than 40% of depressed mothers are prescribed with antidepressants (Lind et al., 2017). On the one hand, SSRI treatment reduces depressive symptoms and improve certain functions needed for adequate maternal care, such as the overall functioning and maternal role functioning (e.g. gratification in the maternal role) (Logsdon et al., 2009, Logsdon et al., 2011). Thus, SSRI use is beneficial for improving maternal care. On the other hand, chronic SSRI treatment is known to induce an up-regulation of the 5-HT2A receptors in the frontal EIPA sale (Hamon and Blier, 2013, Massou et al., 1997). As our findings indicate that enhanced frontal 5-HT2A receptors might be detrimental to maternal behavior, chronic SSRI treatment itself might cause a negative impact on the quality of maternal care. Animal research using postpartum depression models are important in untangling the effects of depression and SSRI treatment on maternal behavior. Taken together, the 5-HT2A receptor plays an important role in the modulation of maternal behavior in rats. We suggest three neural systems where 5-HT2A receptors may achieve this effect. First, the 5-HT2A receptors in the VTA and NAc may modulate the neuronal activity of dopamine neurons and dopamine release to affect incentive aspects of maternal care (Li and Fleming, 2003, Numan, 2007). Second, the 5-HT2A receptors in the mPFC could modulate the glutamatergic and GABAergic neurotransmission and regulate impulsivity and motivation. Finally, the 5-HT2A receptors in the vBNST, CeA and DR may interact with other subcortical structures (e.g. medial preoptic area) to alter maternal behavior. Clinically, our finding that the 5-HT2A receptor is critically important for maternal behavior in rats may have revealed that one possible cause of postpartum mental disorders (e.g. depression and psychosis) is the functional disruption of this receptor system (Guiard and Di Giovanni, 2015, Messa et al., 2003). This idea is supported by the observations that one mechanism of major depression and the antidepressant action of selective serotonin reuptake inhibitors (SSRIs) are mediated by the 5-HT2A receptors (Hamon and Blier, 2013). Future research needs to be conducted to elucidate the exact central mechanisms of 5-HT2A receptor in maternal behavior. This research will shed light on the possible functional dysregulation of the 5-HT2A receptor in postpartum mental disorders. Such knowledge may help inform the development of effective interventions to promote and facilitate maternal care.
    Introduction Serotonin (5-HT) is a monoamine neurotransmitter involved in numerous behavioral and physiological functions. Serotonin mediates its effects through 14 distinct 5-HT receptor subtypes, which are divided into seven families (5-HT1–5-HT7) [1]. The 5-HT2C-receptor subtype is exclusively expressed in the central nervous system where it modulates various behaviors, including feeding and reward. The involvement of 5-HT2C receptors in the regulation of food intake has been suggested by several previous studies [2]. This receptor subtype can be modulated by lorcaserin, a selective 5-HT2C receptor agonist, which was approved for weight loss by the FDA in 2012 under the name of Belviq®. Serotoninergic neurotransmission in the hypothalamus is a major brain mechanism implicated in the homeostatic regulation of energy metabolism as well as in feeding behavior [3]. Stimulation of 5-HT2C receptors in the arcuate nucleus (ARC) of the hypothalamus induces proopiomelanocortin (POMC) release, which in turn is cleaved into α-melanocyte stimulating hormone (α-MSH). α-MSH promotes satiety by acting on the melanocortin 4 receptor (MCR4) in the paraventricular nucleus of the hypothalamus [4]. On the other hand, neurons in the ARC producing Agouti-related protein and neuropeptide Y (NPY) increase food intake by blocking POMC neurons [5]. Hence, 5-HT2C receptor agonists likely regulate the metabolic aspects of food intake by acting directly on these hypothalamic pathways [6]. Nevertheless, engagement or maintenance of feeding behavior is potently influenced by the rewarding properties of food [7]. Evidence in animal models has gradually accumulated over the past decade, to demonstrate that 5-HT2C receptor agonists affect a variety of behaviors and link neurobiological networks related to reward and drug abuse. Recent studies showed neurological and behavioral similarities that overlap between drug addiction and obesity [8].